Device and method for coupling lines to fluidic microsystems

ABSTRACT

A coupling device ( 100 ), particularly for liquid-tight coupling of at least one liquid line ( 10 ) to a fluidic system ( 20 ), is described, which comprises: at least one sealing device ( 30 ), which is implemented to receive an end region ( 11 ) of the liquid line ( 10 ) and has a first sealing surface ( 31 ) for placement on an external surface ( 22 ) of the fluidic system in such a way that the end of the liquid line ( 10 ) is laterally enclosed by the first sealing surface ( 31 ) and points toward an opening ( 23 ) in the external surface ( 22 ), and a clamping device ( 40 ), using which the sealing device ( 30 ) may be pressed against the fluidic system ( 20 ), so that the first sealing surface ( 31 ) produces a liquid-tight connection with the external surface ( 22 ).

BACKGROUND OF THE INVENTION

The invention relates to devices for coupling liquid lines to fluidicmicrosystems, particularly a coupling device for liquid-tight couplingof at least one liquid line to a fluidic system, fluidic systems whichare equipped with devices of this type, and methods for coupling linesto fluidic microsystems.

In biotechnology, analytics, medical research, diagnostics, and forpharmaceutical screening technologies, fluidic systems are used forhandling suspended biological or synthetic samples. Miniaturized fluidicsystems (micro-fluidic systems, fluidic microsystems), having typicaldimensions of fluidic channels or compartments in the sub-millimeterrange, are of special interest. Fluidic microsystems are particularlysuitable for sample-specific single cell treatment or measurement andare equipped with microelectrode devices for this purpose if necessary.Typically, a fluidic microsystem is manufactured as a compact component(chip). The following technologies are known for charging themicrosystems with the particular samples (e.g., biological cells, cellcomponents, synthetic particles, and/or liquid media).

Firstly, receiving samples in pipette tips and applying them via tubingwhich is attached to the microsystem is known. Furthermore, continuouslysupplying microsystems with a transport or envelope stream into whichthe samples are introduced using pumps (e.g., syringe pumps, peristalticpumps, piezoelectric pumps, and the like) is known. To attach tubing,providing permanent adhesive bonds, using plug-in adapters which areattached to the microsystem (see Reichle et al. “BBA”, Vol. 1459, 2000,pp. 218-229), or producing an attachment using screw bushings are known.

Permanent attachment of tubing to microsystems is disadvantageous, sincefor most applications flexible adaptation of the microsystem to thesample supply and separate handling of the tubing and the microsystem,e.g., for cleaning purposes, is desired. The plug-in or screwconnections, in contrast, have disadvantages for producing flow, sincean undesired dead volume is formed at the location of a plug-in or screwadapter, at which the flow cross-section also changes in comparison tothe attached tube.

The formation of a dead volume causes multiple problems. Firstly,quantitative sample introduction or quantitative sample removal is mademore difficult or prevented at low cell counts and/or small samplevolumes (e.g. <10 μl, <1000 cells/μl). The applications of conventionaltube couplings are restricted to microsystems in which volumes in thehigher μl to ml range may be accommodated as reservoir volumes and theflow speeds and volume flows are in the range >100 μl/hour and thespeeds are in the range >500 μm/second and the retrieval rate of thesample assayed is not of overwhelming interest. However, this representsa significant restriction of the field of use of conventionalmicrosystems. Furthermore, every dead volume is connected with extendedpumping times. A tube having an internal diameter of approximately 250μm has a volume of approximately 2 μl for 1 cm of tube length. At adesired flow speed of approximately 10 μl/hour, a dwell time ofapproximately 10 minutes results. With an equal dead volume, anundesired extension of the pumping time accordingly results. If multiplemicrosystems are coupled as required by an application, unacceptableprocess delays result.

It is especially critical that air bubbles may form or may adhere atsubstrate transitions and dead volumes. Particularly in the event ofdiscontinuous operation (“stop and go”), these lead to non-reproduciblepressure changes and thus to disadvantageous movement variations of theparticles or cells in the microsystem.

The dead volume is usually also connected to a change of the flowcross-section, e.g., an expansion at a connection adapter. In the eventof an expansion or accordingly after a narrowing, the flow speed isreduced. Samples or sample components may settle (sedimentation). Forexample, undesired loss of cells or a delay may occur until the cellsare flushed further. Dead volumes therefore also generate a danger dueto accumulation of impurities, through which susceptibility to microbesmay arise.

A coupling device for microfluidic applications is known from WO99/63260. A hollow body is fixed on a fluidic chip, in whose endpointing toward the fluidic chip an O-ring seal is integrated via anopening in the fluidic chip. For coupling, a liquid line having aprofiled external wall is plugged into the hollow body having the O-ringseal. The free end of the liquid line is pushed toward the opening untilthe profiled external wall of the liquid line is seated in the O-ringseal. In this state, the O-ring seal is radially compressed in thehollow body, a liquid-tight connection being formed between the liquidline and the fluidic chip.

The coupling device according to WO 99/63260 has multiple disadvantages.Firstly, the coupling device is only usable with liquid lines having aprofiled line end. The line end must be processed before use ifnecessary (e.g., by removing material or a heat treatment). A furtherdisadvantage arises if, by plugging the end of the liquid line into thefluidic chip, a step arises in the particular opening of the fluidicchip because of the thickness of the wall material of the liquid line,through which the dead volume having the disadvantages described aboveis formed. Furthermore, it is problematic that the conventionaltechnology is designed for relatively high operating pressures (e.g., 70bar), which are impractical, however, in fluidic microsystem technology,in which fragile glass chips are used, for example.

An essential disadvantage is that according to WO 99/63260, a good sealis achieved between the liquid line and the radially clamped O-ring.However, there is only a relatively narrow contact surface between theO-ring and the fluidic chip, whose sealing function is fulfilledunreliably because of its small dimensions. In addition, the surface ofthe fluidic chip is loaded unevenly. High requirements are set on thestability of the fluidic chip. If correspondingly thicker wall materialsare used, disadvantages result for the applicability of opticalmeasurement methods to the fluidic chip.

The problems cited relate not only to the coupling of tubing, but ratheralso generally to other connections between liquid lines (e.g.,capillaries) and fluidic microsystems.

Particularly if microsystems having small intrinsic volumes are usedand/or for problems in cellular biology or medicine, the followingrequirements may arise. Small cell counts in the range from 1 to 500cells are to be flushed through the microsystem with a retrievalrate >70% and are to be analyzed and manipulated therein according todifferent criteria (e.g., size, dielectric properties, opticalproperties, fluorescence properties). In this case, typical pumpingspeeds in the range from 100 to 500 μm/seconds or pump rates in therange from 2-20 μl/hour are to be implemented. Furthermore, it isdesirable for specific applications to retrieve the cellsquantitatively, possibly down to individual cells. For this purpose,applications exist for isolating clones originating from individualcells and for sample preparation for single cell technologies, such assingle cell PCR, single cell CE, or the like, for example.

The object of the present invention is to provide improved devices forcoupling liquid lines to fluidic microsystems, using which thedisadvantages of conventional coupling technologies are overcome. Thedevices are particularly to be distinguished by an expanded field ofapplication, high flexibility, and improved flow-technology properties,such as minimal dead volume and avoidance of steps in the flowcross-section. The object of the present invention is also to provideimproved methods for coupling liquid lines to fluidic microsystems,particularly using devices of this type.

SUMMARY OF THE INVENTION

A basic idea of the present invention is to provide a coupling devicefor liquid-tight coupling of at least one liquid line to a fluidicsystem, particularly to a fluidic microsystems, which includes at leastone sealing device, at which the liquid line ends and which has at leastone bushing having a first planar sealing surface for resting on anouter surface of the fluidic system, through which the end of the liquidline points toward an opening in the outer surface, and at least oneclamping device, using which the sealing device may be pressed againstthe fluidic system, so that the first sealing surface forms aliquid-tight connection with the outer surface of the fluidic system.Providing a sealing device having a sealing surface which radiallyencloses the end of the liquid line has the advantage that the liquidline may be coupled directly to the fluidic system without a deadvolume. The liquid line opens directly into the microsystem without anintermediate adapter. The clamping device provides a detachableconnection between the liquid line and the fluidic system which isadvantageously suitable for sealing even at increased pressures, andthus allows high flow speeds even with small flow cross-sections,without the fluidic system being influenced by the mechanical contactpressure. The coupling device according to the present invention isdistinguished by simplified handling. The liquid line equipped with thesealing device may be used for coupling to a fluidic system on its outersurface, the end of the liquid line being positioned over a selectedopening in the outer surface and being fixed by simple actuation of theclamping device.

According to the present invention, the clamping device has at least onehollow plunger which is movable in relation to the outer surface of thefluidic system, so that through the movement toward the fluidic system,a force directed toward the outer surface of the fluidic system may beexerted on the at least one bushing of the sealing device. The at leastone bushing of the sealing device has an external shape which is formedso that the desired force is exerted on the sealing surface under theeffect of the hollow plunger.

According to a preferred embodiment of the present invention, theclamping device includes at least one hollow plunger which has at leastone receptacle for at least one part of the bushing of the sealingdevice and possibly a front face, using which the sealing device may bepressed against the fluidic system. The use of a hollow plunger has thespecial advantage that the contact pressure for fixing the sealingdevice on the external surface of the fluidic system is distributeduniformly and may be selected as so low in relation to the sealing areathat the fluidic system is not deformed or possibly destroyed.Furthermore, multiple liquid lines, which may be connected to one ormore sealing devices, may advantageously be fixed, using multiplebushings, simultaneously and in a space-saving way using the particularassociated hollow plungers.

The sealing device may be produced integrally with the end of the liquidline or permanently connected thereto (e.g., glued). According topreferred embodiments of the present invention, however, the liquid lineand the sealing device form separate components which are detachablefrom one another and which may be reversibly connected to one another.For this purpose, the bushing of the sealing device has an internalhollow channel which is implemented to detachably receive an end regionof the liquid line and forms a second sealing surface, the sealingdevice being able to be pressed on the end region of the liquid lineusing the clamping device, so that the second sealing surface forms aliquid-tight connection with the surface of the end region of the liquidline. In this design, the sealing device advantageously fulfills adouble function. The end of the sealing line is sealed laterally (orradially) in relation to the outer surface of the fluidic system andcorresponding to the alignment of the liquid line (or axially) along thesurface of the liquid line. The additional advantage of expandedflexibility of the coupling device results with the detachable sealingdevice. The bushing may be plugged onto a tube end without problems andfixed on a fluidic system using the clamping device, particularly thehollow plunger. The length of the liquid line may be optimally tailoredbeforehand to the geometric conditions in the concrete application. Tubelengths may be reduced and pump times may thus be shortened.

According to a further preferred embodiment of the present invention,the hollow plunger of the clamping device forms a conical or cylindricalreceptacle for the bushing of the sealing device, whose maximum internaldiameter is smaller than the external diameter of the sealing device. Acylindrical receptacle has the advantage of uniform contact pressure ofthe sealing device on the end of the liquid line. Using the conicalreceptacle, the first and second sealing surfaces are advantageouslysealed simultaneously when the clamping device is actuated.

According to a further preferred embodiment of the present invention,the at least one sealing device is equipped with multiple bushings,using which multiple liquid lines may be coupled to the fluidic system.The bushings may be connected to one another in one or more sealingunits in rows or in a matrix. An advantage of this embodiment issimultaneous and parallel coupling of multiple liquid lines to thefluidic system.

It is advantageous, both in regard to the alignment of the liquid linein relation to the opening in the external surface of the microsystemand to coupling free of a dead volume, if the internal diameter of theliquid line is smaller than the diameter of the opening in the externalsurface of the fluidic system. The flow cross-section does expand in theregion of the opening at the coupling, but cell losses due to settling,for example, may be prevented at this expansion through the design ofthe microsystem, e.g., through microelectrodes in proximity to theopening.

If the first sealing surface is larger than the cross-sectional area ofthe end of the liquid line, advantages may result for the seal even atlow contact pressure of the clamping device.

A further subject of the present invention is a fluidic system which isequipped with at least one coupling device according to the presentinvention. The fluidic system has a chip body to which at least oneliquid line is connected using the coupling device.

According to a preferred embodiment of the present invention, the chipbody has an external surface which is planar in at least some sections,in which at least one opening is formed, the line end of the liquid linepreferably being seated on the planar external surface. The dead volumeof the coupling may thus advantageously be minimized. Since the line endof the liquid line preferably has the external shape of a circularcylinder, non-profiled tubes or capillaries may advantageously be usedas liquid lines without additional processing steps. No specialprecision requirements must be placed on the external diameter of liquidlines.

Special advantages result if the fluidic system according to the presentinvention includes a fluidic microsystem. The requirements of fluidicmicrosystems in regard to careful mechanical handling and thepossibility of measurements in the microsystem even in proximity to thecoupled lines are optimally fulfilled by the combination with thecoupling device according to the present invention.

A method for liquid-tight coupling of at least one liquid line to afluidic system, particularly using a coupling device according to thepresent invention, is also a subject of the present invention. Themethod is distinguished by a sequence of steps in which at least oneliquid line is coupled to the fluidic system using a sealing device andthe clamping device, so that the end of the liquid line is aligned withan opening in the external surface of the fluidic system, a contactpressure being implemented at the clamping device in such a way that thesealing device forms the liquid-tight connection with the externalsurface of the fluidic system. The method according to the presentinvention has the advantage of simple and universal application fordifferent types of liquid lines of interest in practice. Liquids, e.g.,particle suspensions, are introduced into the microfluidic systemwithout a dead volume, i.e., directly from the liquid line (hollowbody).

The present invention has the following further advantages. The couplingdevice according to the present invention is easily employable by theuser. Due to the planar design of the first sealing surface, a largecontact area to the external surface of the fluidic system results,through which an optimum seal is achieved. This is correspondingly truefor the part of the sealing device projecting into the clamping device,which ensures a large contact surface to the end region of the liquidline. The coupling device is distinguished by uniform pressuredistribution and therefore a low mechanical load of the fluidic system,particularly a fluidic microsystem. The integrity is ensured even atincreased internal pressures. A reliable seal is produced even atinternal pressures of up to, for example, 0.1 MPa. Notwithstanding thesealing forces necessary for this purpose, the coupling device isdetachable reversibly, easily (i.e., without a tool), and in auser-friendly way. The entire coupling device, parts thereof, or acomposite of the coupling device and the lines may be manufactured as adisposable article or sterilized through a suitable method.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

Further advantages and details of the present invention are describedbelow with reference to the attached drawing.

FIG. 1 shows a schematic sectional view of a sealing device according toa preferred embodiment of the coupling device according to the presentinvention,

FIG. 2 shows a schematic illustration of the interaction of the sealingand clamping devices of the coupling device according to the presentinvention,

FIG. 3 shows a perspective view of an embodiment of the coupling deviceaccording to the present invention which is designed for couplingmultiple liquid lines,

FIG. 4 shows a sealing unit of the coupling device according to FIG. 3,

FIG. 5 shows two views of a clamping device of the coupling deviceaccording to FIG. 3,

FIG. 6 shows an altered embodiment of the coupling device according toFIG. 3,

FIG. 7 shows a further altered embodiment of the coupling deviceaccording to FIG. 3,

FIG. 8 shows an illustration of the parts of the coupling deviceaccording to FIG. 7, and

FIG. 9 shows a graph of test results which were obtained using acoupling device according to the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

The coupling device according to the present invention is described inthe following for exemplary purposes with reference to embodiments whichare set up for coupling flexible liquid lines (tubes) to a fluidicmicrosystem. The present invention is not restricted to the designsillustrated, but rather may also be implemented using altered liquidlines and fluidic systems. In general, a liquid line is a hollow body inwhich a liquid sample is positioned and which is set up to introduce thesample into the fluidic system. The liquid line may particularly be atube, a capillary, a part of a syringe, or a connection to a reservoirof a microtitration plate or to a liquid conveyor device.

FIG. 1 partially illustrates a first embodiment of the coupling device100, which is set up for coupling a liquid line 10 to the microsystem 20using a sealing device 30. FIG. 1 is a schematic illustration, thedetails and size ratios able to be varied in practice. The clampingdevice 40, which is part of the coupling device according to the presentinvention, has its function only shown in FIG. 2 for reasons of clarity.The liquid line 10 is, for example, a tube made of plastic, e.g., PTFE,PEEK, polypropylene, polyethylene, PVC, silicone, or a capillary made ofglass, metal, or a metal alloy. The material is selected as a functionof the application and is preferably inert in relation to the samples tobe treated (cell compatible), sterilizable, and not very cell adhesive.The internal diameter of the liquid line 10 is, for example,approximately 250 μm. For cell biology applications, the internaldiameter is preferably in the range from 120 μm to 200 μm or larger. Theexternal diameter of the liquid line 10 is, for example, 1.6 mm.

The microsystem 20, which is only partially shown schematically in FIGS.1 and 2, is formed by a channel or compartment structure in a solid body(chip). The channels 21 of the microsystem have dimensions which aretypically in the range from 5 to 1000 μm (width), 5 to 1000 μm (height),and 1 to 100 mm (length). Biological or synthetic samples, e.g., cells,cell components, macromolecules, plastic particles, or the like areanalyzed, manipulated, separated, and/or microscopically evaluated inthe microsystem (see Müller et al. in “Biosensors & Bioelectronics, Vol.14, 1999, pp. 247-256). For cell biology applications, the dimensions ofthe channel 21 are, for example: 40 μm channel height, 200 to 800 μmchannel width, 20 mm channel length. The microsystem 20 is, depending onits task, equipped in a way known per se with measurement and/ormanipulation devices, particularly with a microelectrode device (notshown) for dielectrophoretic manipulation and/or measurement ofparticles. The microsystem is made, for example, of a semiconductormaterial (e.g. silicon), plastic, or glass, or a mixed composite of atleast two of these materials.

The chip body of the microsystem 20 has an external surface 22 which isflat in at least some sections. Openings 23 are provided in the flatexternal surface 22 for connection to other microsystems or supply ordischarge devices, through which the structure of the channels 21 orcompartments may be accessed. The number and arrangement of openings 23is selected as a function of the task while designing the microsystem.For example, in FIG. 1, a single opening 23 is shown which has adiameter of 500 μm, for example, and which is used for coupling asuspension sample from the liquid line 10 into the channel 21. Ingeneral, the opening forms an inlet or outlet in the wall of the fluidicsystem. In the surroundings of the opening or hole 23, the externalsurface 22 has a flat, smooth surface. The smooth surface is providedper se in most chip materials.

The sealing device 30 includes a conical bushing 32, on whose broaderfront face (bottom in FIG. 1) the first sealing surface 31 is formed. Inthe example shown, the bushing 32 has a lower projection 33. The firstsealing surface 31 is enlarged by the projection 33 and an engagementsurface for the clamping device 40 (see FIG. 2) is additionallyprovided. The projection 33 is, however, not a necessary feature of thepresent invention. The sealing function may also be formed by a simpleconical bushing 32 or, with a suitable internal shape of the clampingdevice 40, by a bushing in the form of a straight cylinder. In general,the external shape of the bushing 32 and the internal shape of theclamping device 40 are produced so that a force may be exerted at leasttoward the external surface of the microsystem. The first sealingsurface 31 has a dimension of at least 10 mm², preferably 20 mm².

The sealing device 30 is made of an elastic plastic material, such assilicone material, rubber, or another elastic plastic, which ispreferably sterilizable, does not swell, and is biologically harmless.The material is preferably so soft that a seal is made possible ininteraction with the clamping device, without deforming or destroyingthe chip body. It has a hardness in the range 30-50 Shore A, forexample.

Preferably, materials are used which have a higher resistance totemperature, solvents (e.g., organic solvent such as ethanol), andnon-ionic, anionic, and cationic surfactants, and/or which allowsterilization of the device through autoclaving (e.g., 20 minutes at121° C. in pressurized water steam at 2 bar).

On the inside, the bushing 32 has a hollow channel 34, which is designedfor removably receiving the end region 11 of the liquid line 10. Thehollow channel 34 forms a second sealing surface 35, which represents acontact surface of the sealing device 30 with the end region 11. Theconical second sealing surface 35 has a dimension of at least 10 mm²,preferably 20 mm². The internal diameter of the hollow channel 34 ispreferably selected so that it is at most as large as the externaldiameter of the end region 11, but is preferably slightly smaller.

To implement the liquid-tight coupling, the sealing device 30 is pressedonto the tubing 10 and to the microsystem 20 using the clamping device40, as is schematically illustrated in FIG. 2. The clamping device 40includes a hollow plunger 41, which may be pressed against themicrosystem 20 using a schematically shown clamping mechanism 42. Thebottom of the hollow plunger 41 is at a distance to the external surface22. When the clamping mechanism 42 is actuated (a bayonet connection,for example, see FIG. 7) the distance of the hollow plunger 41 from theexternal surface 22 is reduced. The exertion of force connectedtherewith occurs perpendicularly to the external surface 22, asindicated by the arrows. The hollow plunger 41 forms a conicalreceptacle 43, whose internal shape is adapted to the external shape ofthe bushing 32. The contact surface between the internal and externalshapes has a dimension of at least 10 mm², preferably 33 mm². When thehollow plunger 41 is pressed against the microsystem 20, the sealingmaterial is compressed and the first and second sealing surfaces 31, 35become liquid-tight. This state is illustrated in FIG. 2.

FIGS. 1 and 2 show, as a special advantage of the coupling deviceaccording to the present invention, that the end 12 of the liquid line10 directly adjoins the opening 23 of the channel 21. Samples aretransferred from the liquid line 10 into the channel 21 without a deadvolume. The liquid line 10 discharges directly into the channel 21without interposing adapters or the like.

The coupling according to the present invention using the couplingdevice 100 is performed according to one of the following procedures,depending on the application and construction of the clamping device 40.Firstly, it is possible to first insert the end region 11 of the liquidline 10 into the bushing 32 of the sealing device 30 and then push thesealing device 30 into the receptacle 43 of the clamping device 40.Subsequently, the clamping device 40 is positioned over the opening 23with the sealing device and fixed on the microsystem 20. Alternatively,it is possible to first position the sealing device 30 with the liquidline 10 inserted over the opening 23 and then attach and tighten theclamping device 40 in order to produce the liquid-tight connection.Finally, the coupling device according to the present inventionalternatively allows first only placing the sealing device 30 over theopening 23 with the clamping device 40, without pressing the clampingdevice 40 onto the microsystem 20, however. In this state, the endregion 11 of the liquid line 10 may be pushed into the bushing 32 andthe clamping device 40 may subsequently be tightened. This method isparticularly advantageous if sealing units which are described belowwith reference to FIGS. 3 through 6 are used.

An altered embodiment of the coupling device 100 according to thepresent invention is shown disassembled in perspective in FIG. 3. Inthis design, multiple liquid lines 10 are coupled to a fluidicmicrosystem 22, two separate sealing units 36 being provided as sealingdevices 30 and a fluidic block 45 being provided as the clamping device40. One or more externally induced liquid flows are conducted intoand/or out of the microfluidic system independently of one another usingthe liquid lines or hollow bodies 10.

The microsystem 20 includes the chip body 24, on which a holding plate25 is placed. The chip body 24 contains the channel or compartmentstructure having a microelectrode device, from which electrical contacts26 are guided to the edge of the chip body 24. The chip body 24 is made,for example, of a glass composite having multiple fluidic openings, eachof which corresponds to the opening 23 in FIG. 1. For example, eightfluidic openings having a diameter of 500 μm each are provided. Theholding plate 25 is provided on the top of the chip body 24 and has tworecesses 27 each of which for receiving a sealing unit 36 and anobservation window 28, through which the glass chip body 24 is exposed.It is a special advantage of the present invention that the couplingdevice has a sufficiently low overall height in the z direction (i.e.,perpendicular to the upper external surface of the chip body 24) thatthe inside of the microsystem 20 may be imaged by an optical microscope.The adjustment of the optical components of the microscope is notobstructed by parts of the coupling device.

Each sealing unit 36 which is shown enlarged in FIG. 4 includes fourconical bushings 32, each of which is constructed analogously to thesealing device 30 shown in FIG. 1 and via which the continuousprojections 33 are connected to one another in series. The continuousprojections 33 form a sealing mat. The intervals of the sealing bushings32 projecting out of the sealing mat into the sealing unit 36 preciselycorrespond to the intervals of the fluidic openings in the chip body 26.The sealing mat has the special advantage that the contact pressuresgenerated by the clamping device are transmitted uniformly onto theexternal surface of the chip body 24.

The fluidic block 45, which is shown in greater detail on two sides inFIG. 5, fulfills the function of the clamping device 40. It includes acarrier plate 46, on whose side facing toward the microsystem 20 tworows of hollow plungers 47 are provided, which simultaneously form tubeguides and receptacles for the sealing units 36. The fluidic block 45 ispreferably made of metal, metal alloys, plastics, such as Teflon, PEEK,Kel-F, or ceramic.

The sealing units 36 are inserted into the hollow plunger rows 47 tocouple the liquid lines 10 to the microsystem 20. This may be performedmanually by exerting a slight pressure. The fluidic block 45 issubsequently placed on the microsystem 20. The bottoms of the sealingunits 36 are received by the recesses 27 in the holding plate 25. Thefluidic block 45 and the microsystem 20 are connected to one another bya mechanical structure (e.g., bayonet connection, see FIG. 7).Subsequently, the liquid lines 10 are inserted into the hollow channelsof the sealing devices and the fluidic block 45 is pressed against themicrosystem. The liquid-tight composite is advantageously producedsimultaneously for all liquid lines. If one or more fluidic openings arenot to be coupled to a line, massive filler bodies, e.g., in the form ofrods, are inserted into the corresponding sealing devices.

An altered construction of the coupling device according to FIG. 3 isillustrated in FIG. 6. In addition to the microsystem 20 having the chipbody 24 and the holding plate 25, a chip carrier (pillar) 48 is shown,which interacts with the fluidic block 45. The reference number 29refers to a circuit board adapter which interacts with the electricalcontacts 26 of the chip body for electrical activation of themicrosystem.

The construction shown in FIG. 6 is assembled as follows. The chip body24 is connected to the holding plate 25 (e.g., glued). The holding plate25 is used to increase the strength of the chip body and for cooling(heat sink). The holding plate 25 is screwed onto the chip carrier 48.It has two parallel oblong holes corresponding to the above-mentionedrecesses 27, between which the observation window 28 is located. Guidepins 49 for aligning the fluidic block on the chip carrier 48 arelocated on the top of the chip carrier 48 and the bottom of the fluidicblock 45. The sealing units 36 positioned between chip carrier 48 andchip body 24 fulfill two tasks, specifically receiving the liquid lines10 and sealing the end sections of the liquid lines.

The microsystem 20 is set up for the purpose of analyzing, separating,and/or isolating molecules or particles in liquids. For example,microobjects, such as cells and artificial particles, typically in theorder of magnitude of 2 μm to 100 μm, are to be analyzed, manipulated,pored, separated, and/or microscopically evaluated. The microsystem 20forms a sorter, for example. For this purpose, the chip body contains atleast one channel having a sorting device, as is known per se in fluidicmicrosystems. It is based, for example, on the dielectric separation ofparticles having different properties measured in the microsystem. Asuspension having a particle mixture is introduced into the channel viaa liquid line. For coupling, the sample is introduced accelerated by anenvelope stream which has a flow speed of up to 2000 pl/seconds, forexample. After the sorting, two partial streams are guided out of themicrosystem, each of which is again accelerated using an envelope streamfor accelerated coupling.

A bayonet connection 42, through which the fluidic block 45 and theholding plate 25 are connected to one another, is shown in FIGS. 7 and 8with reference to a further embodiment of the present invention. Thebayonet connection 42 advantageously forms a coupling and the clampingmechanism schematically shown in FIG. 2 simultaneously, using which thedistance between the cited components may be reduced and the contactpressure may thus be exerted.

The bayonet connection 42 includes a bayonet ring 42.1 having twoanchoring ramps 42.2 and a slot 42.3. The slot 42.3 advantageouslyallows the bayonet ring 42.1 to be put on when the tubing 10 is alreadyinserted into the sealing units 36 by an external auxiliary device (notshown, for example, a sample reservoir or pump). In this case, thetubing 10 is threaded through the slot 42.3 into the bayonet ring 42.1.The anchoring ramps 42.2 work together with two anchor pins 25.1 whichproject from the holding plate 25.

The fluidic block 45 is pressed against the fluidic chip 24 by theholding plate 25 when the bayonet connection 42 is locked. A flat spring(not shown) is advantageously provided between the bayonet ring 42.1 andthe holding plate 25 for this purpose. Alternatively, the movement ofthe bayonet ring 42.1 toward the holding plate 25 may be set by thedesign of the anchoring ramps 42.2.

The fluidic block 45 is equipped in this embodiment with guide pins 45.1which are used to guide and align the bayonet ring 42.1. The guide pins45.1 include projections which are positioned at the corners of thesurface of the fluidic block 45. Furthermore, the holding plate 45 isequipped with lateral openings 45.2, through which the anchor pins 25.1of the holding plate 25 may project.

To assemble the coupling device shown in FIG. 7, the sealing units 36are first placed in the recesses 27 of the holding plate 25 on the chipbody 24 or the sealing units 36 are inserted into the hollow plungerrows 47 of the fluidic block 45 and the fluidic block 45 is then placedon the holding plate 25. Commercially available tubes are inserted intothe addressed openings of the fluidic block. It is advantageously notnecessary for specially equipped tubing having specific diameters orexternal shapes to be used. For example, tubing made of PTFE (externaldiameter 1/16″) are provided. Finally, the bayonet ring 42.1 is placedand locked (by a half rotation, for example). The fluidic block 45 ispressed onto the chip body 24 by the locking motion and the desiredsealing of the inserted tubing is thus achieved.

The embodiment of the present invention shown in FIGS. 7 and 8 has thefollowing further advantages. The bayonet connection 42 may be handledeasily. The fluidic block is reversibly attached to the chip, so thatreplacement of the tubing and the conical sealing mats in particular ismade possible. The tubing and the chip do not require any specialprocessing (grooves, etc.), in order to be sealed, and they may beplugged into the fluidic block while it is in place and do not have tobe inserted before assembly. The breaking danger for the chip when thefluidic block is placed may be reduced to a minimum. Finally, thefluidic block is aligned by the guides mounted on the chip. Tilting ofthe fluidic block by twisting the bayonet closure is prevented by theguide pins.

The result of the test of the coupling device according to the presentinvention is shown in FIG. 9. In the experiment, the speed in thechannel of the microsystem was measured as a function of the pressure inan envelope stream container, using which the speed of the envelopestream is set. With increasing pressure, only a slight oscillation ofthe flow speed in the channel results. The flow in the channel isinfluenced negligibly by the elevation of the flow speed of the envelopestream. This confirms the high integrity of the coupling deviceaccording to the present invention. In contrast to this, in the test ofa conventional coupling device having screw adapters, a strongdependence of the flow speed in the channel on the flow rate of theenvelope stream is observed.

The features of the present invention disclosed in the abovedescription, the drawing, and the claims may be significant for theimplementation of the present invention in its various embodiments bothindividually and in combination.

1. A fluidic system having at least one liquid line and a couplingdevice for liquid-tight coupling the at least one liquid line to asurface of the fluidic system, said fluidic system coupling devicecomprising: at least one sealing device having at least one bushingreceiving an end region of the at least one liquid line and having afirst sealing surface in contact with an external surface of the fluidicsystem, an end of the at least one liquid line being laterally enclosedby the first sealing surface and pointing toward an opening in theexternal surface, and a clamping device having a fluidic block, aholding plate and at least one hollow plunger forming a receptacle forat least a part of the at least one bushing, wherein the clamping devicepresses the bushing onto the fluidic system without the clamping devicecontacting the fluidic system, so that the first sealing surfaceproduces a liquid-tight connection with the external surface, whereinthe at least one hollow plunger is situated so as to be movable inrelation to the external surface, the at least one bushing has anexternal shape that is complementary to and interacts with an internalshape of the at least one hollow plunger of the clamping device in sucha way that a force directed toward the external surface of the fluidicsystem is exerted on the at least one bushing using the at least onehollow plunger, and the at least one bushing has a projection formingthe first sealing surface and an engagement surface for the clampingdevice, wherein the at least one bushing has an internal hollow channelremovably receiving the end region of the at least one liquid line, theinternal hollow channel forming a second sealing surface and the atleast one sealing device being able to be pressed against the end regionof the at least one liquid line using the hollow plunger in such a waythat the second sealing surface produces a liquid-tight connection withthe surface of the end region, and wherein the fluidic block is pressedonto the holding plate using a bayonet connector interengaging theholding plate.
 2. The fluidic system according to claim 1, wherein theat least one hollow plunger forms a conical or a cylindrical receptaclefor the at least one bushing.
 3. The fluidic system according to claim2, wherein the at least one bushing has a conical external shape.
 4. Thefluidic system according to claim 1, wherein the internal hollow channelhas a cylindrical internal shape.
 5. The fluidic system according toclaim 1, wherein the first sealing surface is larger than across-sectional area of the end of the at least one liquid line.
 6. Thefluidic system according to claim 1, wherein said sealing device hasmultiple bushings, the multiple bushings forming at least one sealingunit and to couple multiple liquid lines to the fluidic systemsimultaneously.
 7. The fluidic system according to claim 6, wherein thebushings of the sealing device are connected to one another in rows orin a matrix in the at least one sealing unit.
 8. The fluidic systemaccording to claim 7, wherein the at least one sealing unit forms asealing mat, from which the bushings project.
 9. The fluidic systemaccording to claim 6, wherein the clamping device comprises a fluidicblock and a plurality of hollow plungers, in which hollow plungers ofsaid plurality of hollow plungers are formed in accordance with anarrangement of the bushings of the at least one sealing unit.
 10. Thefluidic system according to claim 6, further comprising a holding platepermanently connected with the fluidic system and arranged forpositioning the at least one sealing unit on the fluidic system.
 11. Thefluidic system according to claim 1, comprising a chip body wherein theat least one liquid line is connected to the chip body by the couplingdevice.
 12. The fluidic system according to claim 11, wherein the chipbody is the external surface of the fluidic system, the external surfacebeing planar at least in some sections and having at least one openingadjoined to a line end of the at least one liquid line.
 13. The fluidicsystem according to claim 12, wherein the line end of the at least oneliquid line has a cylindrical external shape.
 14. The fluidic systemaccording to claim 11, which comprises a fluidic microsystem.
 15. Amethod for liquid-tight coupling of the at least one liquid line to thefluidic system using a coupling device according to claim 1, said methodcomprising: providing the coupling device, forming a composite of the atleast one liquid line with one bushing of the at least one sealingdevice, respectively, the clamping device, and the fluidic system, andactuating the clamping device to produce a contact pressure on theprojection of the bushing in such a way that the sealing device formsthe liquid-tight connection with the external surface of the fluidicsystem.
 16. The method according to claim 15, wherein, to form thecomposite, the end region of the at least one liquid line is pluggedinto a bushing of the at least one sealing device, which was previouslypositioned with the clamping device on the fluidic system, so that theend of the at least one liquid line points toward an opening in theexternal surface of the fluidic system.
 17. The method according toclaim 15, wherein, to form the composite, the end region of the at leastone liquid line is plugged into a bushing of the sealing device, whichis subsequently connected to the clamping device and positioned on thefluidic system, so that the end of the at least one liquid line pointstoward an opening in the external surface of the fluidic system.